Electrical stimulation of excitable body tissue is used as a method of treating various pathological conditions. Such stimulation generally entails making an electrical contact between excitable tissue and an electrical pulse generator through use of one or more stimulation leads. Various lead systems and various techniques for implanting these lead systems in contact with excitable body tissue, and particularly the heart, have been developed.
In order to achieve cardiac pacing, sensing, cardioversion and/or defibrillation, various types of cardiac leads have been developed including epicardial leads, endocardial leads, and coronary sinus leads. For example, a transvenous endocardial lead establishes electrical contact between an electrical pulse generator, such as a pacemaker or implantable cardioverter defibrillator, and a patient's heart through placement of the lead in the venous system. Specifically, a transvenous endocardial lead is passed through a vein, with the assistance of a fluoroscope, into the heart where it may be held in contact with the endocardium by the trabeculae of the heart chamber, such as the ventricle. The safety, efficacy and longevity of an electrical pulse generator depends, in part, on the performance of the associated cardiac lead(s) used in conjunction with the pulse generator.
For example, various properties of the lead and electrodes will result in a characteristic impedance and stimulation threshold. Stimulation threshold is the energy required in a stimulation pulse to depolarize, or “capture,” the heart tissue. A relatively high impedance and low threshold is desired to minimize the current drawn from a pulse generator battery in delivering a stimulation pulse. Maximizing the useful life of the pulse generator battery is important battery has reached the end of its useful life.
One factor that can affect the stimulation threshold, particularly during the first several weeks after implantation of a lead, is the natural immunological response of the body to the lead as a foreign object. The presence of the lead activates macrophages, which attach themselves to the surface of the lead and any electrodes and form multi-nucleated giant cells. These cells, in turn, secrete various substances, such as hydrogen peroxide as well as various enzymes, in an effort to dissolve the foreign object. Such substances, while intending to dissolve the foreign object, also inflict damage to the surrounding tissue. When the surrounding tissue is the myocardium, these substance cause necrosis. These areas of necrosis, in turn, impair the electrical characteristics of the electrode-tissue interface. Consequently pacing thresholds rise. Even after the microscopic areas of tissue die the inflammatory response continues and approximately seven days after implant the multi-nucleated giant cells cause fibroblasts to begin laying down collagen to replace the necrotic myocardium. Eventually, on the order of three weeks after implant, the lead and its electrodes are encapsulated by a thick layer of fibrotic tissue. Typically the inflammatory response ends at this time. The fibrotic encapsulation of the lead and its electrodes, however, remains. Since the fibrotic tissue is not excitable tissue, an elevated stimulation threshold can persist due to the degraded electrical properties of the electrode-tissue interface.
A considerable breakthrough in the development of low threshold electrode technology occurred with the invention of the steroid eluting porous pacing electrode of Stokes U.S. Pat. No. 4,506,680 and related Medtronic U.S. Pat. Nos. 4,577,642, and 4,606,118. Steroid, it is believed, inhibits the inflammatory response by inhibiting the activation of the macrophages. Because they do not form multi-nucleated giant cells, the subsequent release of substances to dissolve the object and which also destroy the surrounding tissue is prevented. Thus the necrosis of any tissue by the inflammatory response is minimized as well as the formation of the fibrotic capsule. Minimizing each of these reactions also minimizes the concomitant deterioration of the electrical characteristics of the electrode-tissue interface. The electrode disclosed in the '680 patent was constructed of porous, sintered platinum or titanium, although carbon and ceramic compositions were mentioned. Within the electrode, a plug of silicone rubber impregnated with the sodium salt of dexamethasone phosphate or a water soluble form of another glucocorticosteroid was placed in a chamber. The silicone rubber plug allowed the release of the steroid through the interstitial gaps in the porous sintered metal electrode to reach into the tissue and prevent or reduce inflammation, irritability and subsequent excess fibrosis of the tissue adjacent to the electrode itself.
Thus, the incorporation of steroid elution permitted pacing leads to have a source impedance substantially lower as compared to leads featuring similarly sized solid electrodes. Leads which elute steroid also presented significantly lower peak and chronic pacing thresholds than similarly sized solid or porous electrodes. One example of a lead which eluted steroid meeting widespread commercial success is the Medtronic Model 5534 CAPSURE Z™ lead. The electrode was fabricated of platinized porous platinum and equipped with an annular shaped monolithic controlled release device (MCRD) loaded with an anti-inflammatory agent soluble in water, e.g. the steroid dexamethasone sodium phosphate. The steroid would elute out of the lead and into the surrounding tissue. This water soluble steroid also was deposited within the pores of the porous platinum electrode.
Incorporating steroid so that it will elute from a lead, however, increased the complexity of lead construction as compared to past, non-steroid eluting leads. For example, leads which elute steroid typically require an MCRD to contain the steroid and to thereafter slowly leach out the water soluble steroid into the surrounding tissue. Typically MCRDs were constructed from silicone rubber. Steroid eluting leads also required an area near the electrode in which to house the MCRD, as well as a high degree of dimensional control over the electrode in order to ensure proper steroid elution. Setting aside a volume near the electrode tip to house the MCRD, however, also tended to increase lead body stiffness in that area. The MCRD typically swells over time as the drug elutes from the polymer structure and is replaced by water and electrolytes.
Since the area of greatest concern for minimizing the immunologic response and fibrotic encapsulation is at the electrode itself, it would be desirable to provide a steroid-eluting electrode having steroid released directly at the electrode-tissue interface. One method for applying a steroid to the surface of an electrode is disclosed in U.S. Pat. No. 5,987,746 to Williams, incorporated herein by reference in its entirety. In this method, a solution mixed from an organic solvent and a steroid that is no more than sparingly soluble in water is applied to a lead. The solution is dried to drive of the organic solvent. The remaining steroid, because it is no more than sparingly soluble in water, will not quickly dissolve away from the electrode surface once in contact with bodily fluids and will remain at the electrode-tissue interface long enough to have a desired pharmacological effect. Advantages of this method include elimination of additional structures for carrying the steroid and the presentation of the steroid directly at the tissue-electrode interface.
One limitation of applying a steroid in solution to an electrode, however, is that the steroid remaining on the electrode surface after the solvent has evaporated generally forms a crystalline coating. The surface morphology of this crystalline coating is generally rough, where the roughness is a function of the crystal growth rate and crystal orientation. When two adjacent crystals impinge, further growth is suppressed. A micro-crack can form at the crystal-crystal boundary due to slight orientational mis-alignment of the crystals. These micro-cracks often propagate under small loads. Upon exposure to fluids, capillary forces cause fluid to enter the micro-cracks. Forces imparted by the fluid within the micro-cracks cause the cracks to dilate and grow in length, resulting in mechanical deterioration of the coating. Thus, a solution-deposited drug coating is generally not well adhered to the electrode surface and may easily flake or brush away during handling of the lead for manufacturing and implant procedures. The amount of steroid remaining on the electrode surface once delivered to an implant site may, therefore, be uncertain. It would be desirable to provide an electrode with a steroid coating that is durable enough to remain well-attached to the electrode surface during lead handling and still have the advantages of steroid elution directly at the electrode-tissue interface with elimination of additional structures required for carrying the steroid.